Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells
Gene expression heterogeneity in the pluripotent state of mouse embryonic stem cells (mESCs) has been increasingly well-characterized. In contrast, exit from pluripotency and lineage commitment have not been studied systematically at the single-cell level. Here we measure the gene expression dynamic...
| Main Authors: | , , , , , |
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| Format: | Article |
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Nature Publishing Group
2018
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| Online Access: | http://hdl.handle.net/1721.1/114774 |
| _version_ | 1811072137727836160 |
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| author | Semrau, Stefan Goldmann, Johanna E. Soumillon, Magali Mikkelsen, Tarjei S. Jaenisch, Rudolf van Oudenaarden, Alexander |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Semrau, Stefan Goldmann, Johanna E. Soumillon, Magali Mikkelsen, Tarjei S. Jaenisch, Rudolf van Oudenaarden, Alexander |
| author_sort | Semrau, Stefan |
| collection | MIT |
| description | Gene expression heterogeneity in the pluripotent state of mouse embryonic stem cells (mESCs) has been increasingly well-characterized. In contrast, exit from pluripotency and lineage commitment have not been studied systematically at the single-cell level. Here we measure the gene expression dynamics of retinoic acid driven mESC differentiation from pluripotency to lineage commitment, using an unbiased single-cell transcriptomics approach. We find that the exit from pluripotency marks the start of a lineage transition as well as a transient phase of increased susceptibility to lineage specifying signals. Our study reveals several transcriptional signatures of this phase, including a sharp increase of gene expression variability and sequential expression of two classes of transcriptional regulators. In summary, we provide a comprehensive analysis of the exit from pluripotency and lineage commitment at the single cell level, a potential stepping stone to improved lineage manipulation through timing of differentiation cues. |
| first_indexed | 2024-09-23T09:01:29Z |
| format | Article |
| id | mit-1721.1/114774 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T09:01:29Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1147742022-09-30T12:53:12Z Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells Semrau, Stefan Goldmann, Johanna E. Soumillon, Magali Mikkelsen, Tarjei S. Jaenisch, Rudolf van Oudenaarden, Alexander Massachusetts Institute of Technology. Department of Biology Jaenisch, Rudolf Gene expression heterogeneity in the pluripotent state of mouse embryonic stem cells (mESCs) has been increasingly well-characterized. In contrast, exit from pluripotency and lineage commitment have not been studied systematically at the single-cell level. Here we measure the gene expression dynamics of retinoic acid driven mESC differentiation from pluripotency to lineage commitment, using an unbiased single-cell transcriptomics approach. We find that the exit from pluripotency marks the start of a lineage transition as well as a transient phase of increased susceptibility to lineage specifying signals. Our study reveals several transcriptional signatures of this phase, including a sharp increase of gene expression variability and sequential expression of two classes of transcriptional regulators. In summary, we provide a comprehensive analysis of the exit from pluripotency and lineage commitment at the single cell level, a potential stepping stone to improved lineage manipulation through timing of differentiation cues. National Science Foundation (U.S.) (Grant HD 045022) National Institutes of Health (U.S.) (Grant RO1-CA084198) 2018-04-18T14:52:28Z 2018-04-18T14:52:28Z 2017-10 2016-09 2018-04-09T21:56:03Z Article http://purl.org/eprint/type/JournalArticle 2041-1723 http://hdl.handle.net/1721.1/114774 Semrau, Stefan et al. “Dynamics of Lineage Commitment Revealed by Single-Cell Transcriptomics of Differentiating Embryonic Stem Cells.” Nature Communications 8, 1 (October 2017): 1096 © 2017 The Author(s) http://dx.doi.org/10.1038/S41467-017-01076-4 Nature Communications Creative Commons Attribution 4.0 International License http://creativecommons.org/licenses/by/4.0/ application/pdf Nature Publishing Group Nature |
| spellingShingle | Semrau, Stefan Goldmann, Johanna E. Soumillon, Magali Mikkelsen, Tarjei S. Jaenisch, Rudolf van Oudenaarden, Alexander Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells |
| title | Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells |
| title_full | Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells |
| title_fullStr | Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells |
| title_full_unstemmed | Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells |
| title_short | Dynamics of lineage commitment revealed by single-cell transcriptomics of differentiating embryonic stem cells |
| title_sort | dynamics of lineage commitment revealed by single cell transcriptomics of differentiating embryonic stem cells |
| url | http://hdl.handle.net/1721.1/114774 |
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